U.S. Pat. Nos. 4,292,302, 4,292,303, 4,289,749 and 4,294,820 describe a polymeric diffusion matrix in which there is dispersed terbutaline, clonidine, phenylpropanolamine and phenylephrine, respectively. These four patents in the name of Alec D. Keith et al and commonly assigned to Key Pharmaceuticals, Inc. differ only in having different drugs, the incorporation of which is described in each patent. As will be more completely described below, the polymeric drug diffusion matrix of the Keith et al patents suffers the drawback of being unstable with respect to the water and humectant included therein. Put otherwise, the drug diffusion matrix of the Keith et al patents tends to synerese, i.e. to exude the liquid, water component of the gel.
U.S. Pat. No. 4,460,562 also to Keith, et al titled "Polymeric Diffusion Matrix Containing Propranolol" describes diffusion matrix comprising from about 1 to about 60% of a polar plasticizer (e.g., glycerol), from about 6 to about 30% by weight of at least 90% hydrolyzed polyvinyl alcohol having a molecular weight of about 50,000 to about 150,000, from about 2 to about 30% by weight polyvinyl-pyrrolidone having a molecular weight of about 15,000 to about 85,000 and a pharmaceutically transdermally effective amount of propranolol. As is more completely discussed in the examples this material has inferior adhesion to skin, does not have good elongation and also tends to synerese. Furthermore, the materials of the Keith et al patents are not pressure sensitive adhesives.
The present invention tends to overcome the problems exhibited by the prior art (Keith et al) polymeric diffusion matrices to provide an advantageously skin-compatible, solid, gel (or hydrogel), biomedical adhesive composition.